Once every four days — at a cost of $1,000 each — Randy Curtis injects himself with a drug-filled needle to stanch the bleeding that a single gene mutation sets off inside his body.

A lifetime of drug treatments for hemophiliacs such as Curtis can total upwards of $20 million, not counting the cost to treat, repair or replace elbows, ankles and knees pummeled by years of stress caused by blood flowing into the joints’ cavities.

In the next five years, that could change. A handful of Bay Area companies are working on single-shot gene therapies that could revolutionize treatments for people with hemophilia, AIDS and a host of other maladies by tweaking just one gene, just one time.

The potential to clear a person’s body of a disease or condition with just a single drug injection has even typically cautious biotech executives muttering the word “cure.”

But at what price comes that cure? Are companies justified in charging huge prices for one-time therapies that potentially save millions of dollars per patient and billions for the health care system as a whole? And, just as importantly, what price will insurers, their business customers, and government programs be willing to bear?

Those questions are coming to the fore against the backdrop of a payer revolt against Gilead Sciences Inc.’s hepatitis C drug Sovaldi. It can cure the disease at $1,000 per pill or $84,000 for a 12-week course.

Gene therapies may be even pricier. Some may cost $1 million or more. But after seeing hemophiliacs crippled by the condition despite years of treatment, 59-year-old Curtis would not hesitate to take a single-shot drug to rid himself of hemophilia once and for all.

“In a heartbeat,” he said.

Closing in

One thing is for sure: More gene therapies are moving closer to use, and more venture capital is flowing to gene therapy startups.

Just one gene therapy is approved in Europe — UniQure’s Glybera, a treatment for a rare genetic disorder called lipoprotein lipase deficiency. A head and neck cancer treatment was approved in China in 2003.

No gene therapies are approved for use in the United States. But gene-editing technology from Richmond’s Sangamo BioSciences Inc., aimed at modifying the “doorknob” turned by the AIDS virus, is in the second phase of the three-part Food and Drug Administration drug approval process.

What’s more, San Rafael-based rare disease drug developer BioMarin Pharmaceutical Inc. and San Francisco’s Avalanche Biotechnologies Inc. and Audentes Therapeutics Inc., as well as University of California and Stanford University researchers, are working on various gene therapies targeting a range of rare diseases.

“The objective is one time and you’re done,” said BioMarin CEO Jean-Jacques Bienaimé, whose company plans to start in-human testing of its hemophilia A gene therapy in the second quarter of 2015.

Some experimental gene therapies — such as BioMarin, Avalanche and Audentes — use a virus stripped of its disease-causing payload to deliver a gene that is otherwise missing or whose DNA instructions are unreadable by a cell.

Others, such as Sangamo, make strategic cuts in DNA and insert a correct gene sequence before infusing patients with blood carrying the corrected gene.

How long such treatments will last — a lifetime? a decade? a year? — literally could be the $1 million question. The longer lasting the effect, the more a company would be able to charge.

Most, if not all, gene therapies so far target single-gene mutations such as those spotted in many rare diseases.

“In many larger diseases, it’s not that straightforward,” said Matthew Patterson, president and CEO of Audentes, which is pursuing a gene therapy for X-linked myotubular myopathy, a muscle-weakening disease that typically kills one in every 50,000 newborn boys by the time they reach age two.

Audentes raised $30 million in July from OrbiMed Advisors, 5AM Ventures and Versant Ventures.

Gene therapies could be revolutionary for those rare-disease patients, extending their lives or rescuing them from daily, weekly or monthly treatments. But how does a company price that value?

A gene therapy that extends and improves quality of life may be perceived as more valuable than one — like Bayer HealthCare’s Kogenate FS, which Curtis injects — that has the same effect as an already-approved drug but moves a patient from a lifetime of treatments to a single or limited number of shots, said Douglas Paul, vice president and partner of Medical Marketing Economics LLC, a health care market research firm in Oxford, Miss.

What’s more, Sangamo CEO Edward Lanphier said, value often is in the eye of the beholder.

“If it provides a lifetime functional cure for the disease so a person no longer has to take medicine for the disease or (deal with) any side effects, that’s one sense of value,” Lanphier said. “If it’s not permanent or durable and you still have breakouts, that’s a different value proposition.”

Sangamo expects data from its Phase II HIV gene-editing trial in early 2015.

The debate around Sovaldi, the hepatitis C drug from Foster City-based Gilead Sciences, could presage discussions about the price of gene therapies. Although not a gene therapy, Sovaldi costs $84,000 for 12 weeks of treatment, essentially killing a virus that can cause chronic health problems leading to liver cancer and transplants.

Until Sovaldi’s approval in December, most hepatitis C patients were treated wtih interferon and ribavirin, which have nasty side effects such as flu-like symptoms, fatigue and a lower number of infection-fighting white blood cells.

Sovaldi’s cost is overwhelming to insurers, not so much because of the $84,000 tab itself but because it would be multiplied by the 3 million to 4 million hepatitis C patients in the United States, said Dr. Steve Miller, chief medical officer of Express Scripts, a St. Louis-based prescription benefits manager.

“It’s never been 3 million Americans times $100,000” for a treatment, Miller said. “Payers have been screaming about this (for years), but no one has been listening because, in aggregate, the numbers (with rare diseases were) small.”

Searching for solutions

Yet, for patients, a quick, get-it-now cure is compelling.

Hemophilia patient Curtis, who holds a bachelor’s degree in genetics and a master’s in computer information systems, is the project manager for the largest ongoing U.S. cost-of-care study, at the University of Southern California. Related to the study, a survey asked hemophilia patients if they would take a one-injection cure if they knew there was a one-in-100 chance of painless death overnight.

“If they said, ‘yes,’ then you start ratcheting it down to one-in-75, one-in-50, until it’s 50-50 — and you’ve got guys picking that,” Curtis said. “Certain members of the community are so profoundly impacted by disease, they’d be willing to take that kind of theoretical risk.”

Curtis was infected with hepatitis C and exposed to HIV, though he has a genetic block to the AIDS virus, while taking blood transfusions for hemophilia in the 1970s and early 1980s. Just before Christmas, he completed a 48-week regimen of Vertex Pharmaceuticals’ Incivek, along with interferon and ribavirin that expunged the hepatitis C virus.

Along with additional drugs to counteract side effects, Curtis estimated that the total cost of his nearly one year of treatment was about $80,000.

“It’s still cheaper than a liver transplant,” he said.

For companies, gene therapy pricing is an open book and a potential public relations pitfall. Some gene therapies may cost around $50,000 — similar to many traditional drugs today — but others may hit $1 million. Those eye-popping prices raise thorny issues around who will pay for what and when, particularly when even gene-therapy companies are unsure whether a “one-time” treatment might need to be repeated years or decades later.

One solution, Sangamo’s Lanphier said, is a sort of pay-for-performance model. The drug developer would receive a “sizable” upfront payment but also ongoing cash if a hemophilia patient, for example, didn’t need to take other drugs.

“Sangamo should get some percentage of the value to the system (as well as) the value for some finite period of time (because) the kid didn’t have to go to the hospital to get an infusion when he’s playing soccer,” Lanphier said.

Over time, the health care system still would pay less for a gene therapy treatment for hemophilia than it would with today’s drugs, Lanphier said, “and the person would have a normal life.”

Such a payment plan is attractive to BioMarin’s Bienaimé, for one, because companies won’t have a lifetime of data at the time a gene therapy wins FDA approval. A gene therapy may provide a lifelong cure, but it may need a booster over a certain period of time or its benefit may fizzle out after a few years.

“We want to be able to claim it’s once in a lifetime,” Bienaimé said, but getting FDA approval to say that will be near impossible without lifetime data. “Still, it’s better than (a shot) two or three times a week.”

New payment models

The United Kingdom’s National Institute for Health and Care Excellence is an example of a state-operated entity that grades the quality of additional years of life attributed to a drug. It prices the drug according to a related formula. In the United States, that is a politically charged area, bringing cries of “death panels” and images of callous government bureaucrats allowing Grandma to die because a treatment is judged too expensive for an elderly patient.

“Americans are uncomfortable with this, but we need to figure out fair compensation and not stifle innovation,” Express Script’s Miller said.

In a single-payer system, such as Europe, it may be easier for a drug developer to get reimbursed for a therapy, even a $1 million gene therapy, said Medical Marketing Economics’ Paul. But in the United States, other challenges exist. For example, patients shift insurers as they move from job to job, so one insurer’s cost for a gene therapy may be another insurer’s free ride.

Still, Paul noted, insurers already cover one-time, life-saving surgeries that cost $50,000 or more. A hurdle, he said, is that health care payments are linked to medical events; there is no blanket process for reimbursing a high-priced drug over a period of years while showing that the drug still has benefit.

“Payers will accept the higher prices in many of these diseases,” Paul said, “and there may be new payment methods that evolve as a result.”